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Chemical Structure| 23156-27-6 Chemical Structure| 23156-27-6

Structure of 23156-27-6

Chemical Structure| 23156-27-6

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Product Details of [ 23156-27-6 ]

CAS No. :23156-27-6
Formula : C6H4F2N2O2
M.W : 174.11
SMILES Code : NC1=C(F)C=C(C=C1F)[N+]([O-])=O
MDL No. :MFCD03094274
InChI Key :WDFFWUVELIFAOP-UHFFFAOYSA-N
Pubchem ID :2774175

Safety of [ 23156-27-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 23156-27-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 39.58
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

71.84 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.01
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

1.27
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

2.3
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

1.15
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-0.14
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.12

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-2.02
Solubility 1.65 mg/ml ; 0.00947 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-2.38
Solubility 0.73 mg/ml ; 0.00419 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-1.97
Solubility 1.85 mg/ml ; 0.0106 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

High
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

Yes
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-6.46 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

1.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

3.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.9

Application In Synthesis of [ 23156-27-6 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 23156-27-6 ]

[ 23156-27-6 ] Synthesis Path-Downstream   1~11

YieldReaction ConditionsOperation in experiment
The 3,5-difluoro-4-cyanophenol can be obtained by nitrating 2,6-difluoroaniline, diazotizing the resulting 4-nitro-2,6-difluoroaniline, decomposing the diazonium salt in the presence of a cuprous cyanide to obtain 4-nitro-2,6-difluoro-1-cyanobenzene, reducing the product to obtain 4-cyano-3,5-difluoroaniline, and decomposing its diazonium salt in sulfuric acid.
  • 3
  • [ 32315-10-9 ]
  • [ 1668599-81-2 ]
  • [ 23156-27-6 ]
  • [ 1621684-23-8 ]
YieldReaction ConditionsOperation in experiment
29% A suspension of 3-[4-(1 ,3-benzoxazol-2-yl)piperazin-1 -yl]propyl-N-(2,6-difluoro-4-nitro- phenyl)carbamate (125 mg, 0.271 mmol) and 10% Pd/C (125 mg) in DCM (2.5 mL) and EtOH (2.5 mL) was hydrogenated at room temperature for 4 days. The mixture was filtered and concentrated under reduced pressure. The residue was purified by preparative HPLC to afford compound 7 3-[4-(1 ,3-benzoxazol-2-yl)piperazin-1 - yl]propyl-N-(2,6-difluoro-4-amino-phenyl)carbamate (4.4 mg, 3.7%). ESI-MS m/z: 432 ([M+H]+) 100%); RT =9.38 min (Method 2B).
  • 4
  • [ 32315-10-9 ]
  • [ 1621684-24-9 ]
  • [ 23156-27-6 ]
  • [ 1621684-25-0 ]
YieldReaction ConditionsOperation in experiment
35% A solution of triphosgene (127 mg, 0.43mmol, 0.5 eq.) and <strong>[23156-27-6]2,6-difluoro-4-nitroaniline</strong> (347 mg, 0.86 mmol, 1 eq.) in dry DCM (5 mL) was stirred at 0 <C under an inert atmosphere for 1 hour. After a solution of triethylamine (0.48 mL, 3.44 mmol, 4 eq.) in dry DCM (4 mL) was added, the mixture was stirred at room temperature for 1 hour before a solution of 1 -[4-(1 ,3-benzothiazol-2-yl)piperazin-1 -yl]-3-hydroxy-propan-1 -one (250 mg, 0.86mmol, 1 eq.) in dry DCM (5 mL) was added . The reaction was stirred at room temperature for 20 hours before water (10 mL) was added. The mixture was extracted with ethyl acetate (3X15 mL) and the combined organic phases were dried over MgS04and concentrated under reduced pressure. The residue was purified by preparative flash silica chromatography (from ethyl acetate : hexane = 50 : 50 till 100% ethyl acetate) to afford [3-[4-(1 ,3-benzothiazol-2-yl)piperazin-1 -yl]-3-oxo-propyl] N-(4- nitro-2,6-difluoro-phenyl)carbamate (150 mg, 35%). ESI-MS m/z: 492 ([M+H]+), 100%); RT= 5.08 min (Method 4).
  • 5
  • [ 32315-10-9 ]
  • [ 1621684-17-0 ]
  • [ 23156-27-6 ]
  • [ 1621684-18-1 ]
YieldReaction ConditionsOperation in experiment
16% A solution of triphosgene (1 18 mg, 0.40 mmol, 0.75 eq.) and <strong>[23156-27-6]2,6-difluoro-4-nitroaniline</strong> (140 mg, 0.81 mmol, 1 .5 eq.) in dry DCM (10 mL) was stirred at 0C under an inert atmosphere for 15 min and then allowed to warm up to room temperature. After a solution of triethylamine (0.25 mL) was added, the mixture was stirred at room temperature for 1 hour before a solution of 3-[1 -(1 ,3-benzothiazol-2-yl)-4- piperidyl]propan-1 -ol (149 mg, 0.54 mmol, 1 eq.) in dry DCM (10 mL) and dry THF (10 mL) was added . The reaction was stirred at room temperature for 12 h before water (20 mL) was added. The mixture was extracted with ethyl acetate (3X20 mL) and the combined organic phases were dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by preparative HPLC to afford 3-[4-(1 ,3- benzothiazol-2-yl)piperidyl]propyl-N-(2,6-difluoro-4-nitro-phenyl)carbamate (41 mg, 16%). ESI-MS m/z: 277 ([M+H]+) 100%) ; RT = 5.83 min.
  • 6
  • [ 1668599-81-2 ]
  • [ 23156-27-6 ]
  • [ 1621684-14-7 ]
  • 7
  • [ 1621684-24-9 ]
  • [ 23156-27-6 ]
  • [ 1621684-15-8 ]
  • 8
  • [ 1621684-17-0 ]
  • [ 23156-27-6 ]
  • [ 1621684-09-0 ]
  • 9
  • [ 66684-58-0 ]
  • [ 23156-27-6 ]
YieldReaction ConditionsOperation in experiment
31% With ammonia; In methanol; at 80℃; for 48h; A solution of 3, 4, 5-trifluoro-1 -nitrobenzene (5 g, 28.4 mmol) in a 7N ammonia methanolic solution (30 mL) was stirred at 80 ^ for 2 days. After the mixture was allowed to cool down, water (50 mL) was added and the washed with ethyl acetate (3X100 mL). The organic phases were combined and washed with water (2X50 mL), dried over MgS04 and concentrated under reduced pressure. The product was purified by flash silica chromatography (ethyl acetate : hexane = 20 : 80) to afford 2,6-difluoro- 4-nitroaniline (1 .53 g, 31 %). ESI-MS m/z: 196 ([M+Na]+ , 100%); H NMR (600 MHz, DMSO-d6) delta ppm: 7.82-7-95 (m, 2 H), 6.86 (s, 2 H).
  • 10
  • [ 97-65-4 ]
  • [ 23156-27-6 ]
  • 1-(2,6-difluoro-4-nitrophenyl)-5-oxopyrrolidine-3-carboxylic acid [ No CAS ]
  • 11
  • [ 97-65-4 ]
  • [ 23156-27-6 ]
  • methyl 1-(2,6-difluoro-4-nitrophenyl)-5-oxopyrrolidine-3-carboxylate [ No CAS ]
 

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